Multi Orifice Continuous Subcutaneous Insulin Infusion Catheter with Reduced Pharmacokinetic Variability and Rapid On Off Pharmacodynamic Actions

PROJECT SUMMARY ABSTRACT Over US patients on continuous subcutaneous insulin infusion CSII pump therapy are required to change their infusion site every days Many patients attempt to use their infusion catheters for longer durations resulting in poorer blood glucose control after day of site use and an increased risk for hyperglycemia due to infusion failure Unfortunately insulin absorption by the surrounding subcutaneous tissue varies from day to day and dose to dose and may become temporarily or permanently impaired on any day of catheter use We aim to develop an optimized CSII catheter that will allow for more consistent and reliable insulin absorption pharmacokinetics or PK with rapid on and rapid off actions pharmacodynamics or PD More predictable and consistent insulin absorption will enable patients to achieve improved blood glucose control with longer use of each infusion site We hypothesize that a CSII catheter with multiple orifices along the catheterandapos s shaft will deliver insulin into the subcutaneous tissue in a cylinder shape providing a much larger surface area than the flattened sphere shape of insulin depots produced by conventional single orifice catheters The larger surface area accesses more capillary and lymph vessels allowing for more rapid and uniform insulin uptake into the circulation Furthermore the catheterandapos s design and insertion method will reduce tissue trauma and inflammation Minimizing tissue damage and the immune response will further reduce insulin absorption variability Success of this feasibility study will support further development of multiple orifice CSII catheters made of both steel and soft polymers e g Teflon with automated insertion methods In this SBIR Phase study we will construct prototype CSII catheters by laser drilling holes into a small diameter stainless steel spinal needle with an atraumatic pencil point tip The performance of this prototype catheter will be compared to a commercial catheter in a study of swine for days We will evaluate the flow of insulin through the prototype catheterandapos s holes into the adjacent vascular tissue using micro CT imaging with an insulin x ray contrast agent histology of tissue stained for insulin and glucose clamp insulin PK PD studies The histology data and the micro CT imaging data will be used to correlate the distribution of insulin within the subcutaneous tissue D shape volume and surface area with the PK PD actions of a insulin lispro bolus This pilot animal data will demonstrate how well the device distributes insulin to a larger volume of tissue and reduces tissue trauma Subsequent SBIR Phase funding will support human studies demonstrating the improved efficacy of insulin absorption PROJECT NARRATIVE PUBLIC HEALTH STATEMENT Emerging artificial pancreas systems pair a continuous glucose monitor with an insulin pump and promise to simplify the lives of over M people with Type diabetes in the United States A key barrier to broader adoption of these systems is the day to day variability in insulin response and the day limit on use of current insulin infusion catheters This research aims to understand why insulin response varies and make a more reliable long lasting catheter